TY - JOUR
T1 - Kidney function measures and cardiovascular outcomes in people with diabetes
T2 - the Hoorn Diabetes Care System cohort
AU - Dal Canto, Elisa
AU - Elders, Petra J. M.
AU - van der Heijden, Amber A.
AU - van Ballegooijen, Adriana J.
AU - Lissenberg-Witte, Birgit I.
AU - Rutters, Femke
AU - Beulens, Joline W. J.
N1 - Funding Information: JWJB is supported by a ZonMw VIDI grant (9171 8304). EDC is supported by two grants from the Dutch Heart Foundation (Early HFpEF Young Investigator grant number 30982412 and ShePredicts Investigator grant number 30982441). Funding Information: We acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative that receives support from the Dutch Heart Foundation (CVON2016-Early HFPEF). Some of the data were presented as abstracts at the EASD Annual Meeting, 2021, and at the ADDRM Meeting, 2021. The authors thank the other investigators, staff and participants of the Hoorn Diabetes Care System cohort for their valuable contributions. Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - Aims/hypothesis: Both manifestations of kidney disease in diabetes, reduced eGFR (ml/min per 1.73 m2) and increased urinary albumin/creatinine ratio (UACR, mg/mmol), may increase the risk of specific CVD subtypes in adults with diabetes. Methods: We assessed the prospective association between annually recorded measures of eGFR and UACR and the occurrence of myocardial infarction (MI), CHD, stroke, heart failure (HF) and cardiovascular mortality in 13,657 individuals with diabetes (53.6% male, age 62.3±12.1 years) from the Hoorn Diabetes Care System cohort, using data obtained between 1998 and 2018. Multivariate time-dependent Cox regression models adjusted for cardiovascular risk factors were used to estimate HRs and 95% CI. Associations of eGFR were adjusted for UACR values and vice versa. Effect modification by sex was investigated for all associations. Results: After a mean follow-up period of 7 years, event rates per 1000 person-years were 3.08 for MI, 3.72 for CHD, 1.12 for HF, 0.84 for stroke and 6.25 for cardiovascular mortality. Mildly reduced eGFR (60–90 ml/min per 1.73 m2) and moderately to severely reduced eGFR (<59 ml/min per 1.73 m2) were associated with higher risks of MI (HR 1.52; 95% CI 1.10, 2.12 and HR 1.69; 95% CI 1.09, 2.64) and CHD (HR 1.67; 95% CI 1.23, 2.26 and HR 2.01; 95% CI 1.34, 3.02) compared with normal eGFR (>90 ml/min per 1.73 m2). Mildly reduced eGFR was associated with a higher risk of stroke (HR 2.53; 95% CI 1.27, 5.03). Moderately increased UACR (3–30 mg/mmol) and severely increased UACR (>30 mg/mmol) were prospectively associated with a higher cardiovascular mortality risk in men and women (HR 1.87; 95% CI 1.41, 2.47 and HR 2.78; 95% CI 1.78, 4.34) compared with normal UACR (<3 mg/mmol). Significant effect modification by sex was observed for the association between UACR and HF. Because there were a limited number of HF events within the category of UACR >30 mg/mmol, categories were combined into UACR <3.0 and >3.0 mg/mmol in the stratified analysis. Women but not men with UACR >3.0 mg/mmol had a significantly higher risk of HF compared with normal UACR (HR 2.79; 95% CI 1.47, 5.28). Conclusions/interpretation: This study showed differential and independent prospective associations between manifestations of early kidney damage in diabetes and several CVD subtypes, suggesting that regular monitoring of both kidney function measures may help to identify individuals at higher risk of specific cardiovascular events. Graphical abstract: [Figure not available: see fulltext.].
AB - Aims/hypothesis: Both manifestations of kidney disease in diabetes, reduced eGFR (ml/min per 1.73 m2) and increased urinary albumin/creatinine ratio (UACR, mg/mmol), may increase the risk of specific CVD subtypes in adults with diabetes. Methods: We assessed the prospective association between annually recorded measures of eGFR and UACR and the occurrence of myocardial infarction (MI), CHD, stroke, heart failure (HF) and cardiovascular mortality in 13,657 individuals with diabetes (53.6% male, age 62.3±12.1 years) from the Hoorn Diabetes Care System cohort, using data obtained between 1998 and 2018. Multivariate time-dependent Cox regression models adjusted for cardiovascular risk factors were used to estimate HRs and 95% CI. Associations of eGFR were adjusted for UACR values and vice versa. Effect modification by sex was investigated for all associations. Results: After a mean follow-up period of 7 years, event rates per 1000 person-years were 3.08 for MI, 3.72 for CHD, 1.12 for HF, 0.84 for stroke and 6.25 for cardiovascular mortality. Mildly reduced eGFR (60–90 ml/min per 1.73 m2) and moderately to severely reduced eGFR (<59 ml/min per 1.73 m2) were associated with higher risks of MI (HR 1.52; 95% CI 1.10, 2.12 and HR 1.69; 95% CI 1.09, 2.64) and CHD (HR 1.67; 95% CI 1.23, 2.26 and HR 2.01; 95% CI 1.34, 3.02) compared with normal eGFR (>90 ml/min per 1.73 m2). Mildly reduced eGFR was associated with a higher risk of stroke (HR 2.53; 95% CI 1.27, 5.03). Moderately increased UACR (3–30 mg/mmol) and severely increased UACR (>30 mg/mmol) were prospectively associated with a higher cardiovascular mortality risk in men and women (HR 1.87; 95% CI 1.41, 2.47 and HR 2.78; 95% CI 1.78, 4.34) compared with normal UACR (<3 mg/mmol). Significant effect modification by sex was observed for the association between UACR and HF. Because there were a limited number of HF events within the category of UACR >30 mg/mmol, categories were combined into UACR <3.0 and >3.0 mg/mmol in the stratified analysis. Women but not men with UACR >3.0 mg/mmol had a significantly higher risk of HF compared with normal UACR (HR 2.79; 95% CI 1.47, 5.28). Conclusions/interpretation: This study showed differential and independent prospective associations between manifestations of early kidney damage in diabetes and several CVD subtypes, suggesting that regular monitoring of both kidney function measures may help to identify individuals at higher risk of specific cardiovascular events. Graphical abstract: [Figure not available: see fulltext.].
KW - Cardiovascular disease
KW - Diabetes
KW - Kidney function
KW - Time-dependent Cox regression
UR - http://www.scopus.com/inward/record.url?scp=85141589415&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00125-022-05826-y
DO - https://doi.org/10.1007/s00125-022-05826-y
M3 - Article
C2 - 36347992
SN - 0012-186X
JO - Diabetologia
JF - Diabetologia
ER -